CN1227219C - Guanidinium based biocidal polymers - Google Patents

Abstract

The invention relates to biocidal polymers with a guanidine salt base, characterised in that they are representatives of the series of polyoxyalkylene guanidines and their salts and in that they represent a product of the polycondensation of the guanidine salt with diamines containing polyoxyalkylene chains between two amino groups. Apart from having a strong bactericidal effect, these novel polymer products have relatively low toxicity and high hydrophilicity, dissolve quickly and completely in water and have high relative molecular mass values and distinctive characteristics of polymeric surface-active substances.

Description

Guanidinium based biocidal polymers

The present invention relates to biocidal polymers based on guanidinium salts for use as fungicides in pharmaceuticals, veterinary medicine, waste water treatment, household goods and in all areas of the economy where biocidal preparations are required. In addition, the present invention also relates to processes for the preparation of such salts.

The object of the present invention is to produce homogeneous and pure guanidinium salt based high molecular weight disinfectants which offer low toxicity, high biocidal activity, greater relative molecular mass (Molekularmasse), higher hydrophilicity and surface active substances characteristic.

This is achieved by means of guanidine derivatives, which are products of the polycondensation reaction of acid addition salts of guanidine and diamines which have a polyoxyalkylene chain between two amino groups.

Such products can be prepared according to the invention by polycondensation of a liquid diamine with a guanidinium salt in a liquid diamine medium with continuous mixing at elevated temperature from the start of the reaction until the completion of the reaction, depending on the diamine used, Polycondensation 9-16 hours.

According to the invention, the reaction is ensured by continuous mixing in the liquid phase during the synthesis from the beginning to the end of the reaction. Therefore, the method provides the required homogenization of the system, the required molar ratio relationship of reactants during the reaction, that is, high product quality, simplified technical equipment of the process, and easy realization of production safety requirements.

In particular, for example, triethylene glycol diamine having a relative molecular mass of 148 and polyoxyalkylene diamines of various compositions are reacted with acid addition salts of guanidine. Here, numerous polycationic biocidal polymers with high activity and low toxicity can be prepared. These polymers can be used as fungicides in almost every field.

Suitable acid addition salts of guanidines for polycondensation with triethylene glycol diamine and polyoxyalkylene diamines are salts of inorganic and organic acids, such as hydrochloride, dihydrogen phosphate, carbonate , Sorbate, Nitrate, Hydroacetat, Gluconate, Citrate and Silicate.

The recommended diamine is a liquid with high hydrophilicity, low volatility, and relatively low vapor pressure, ensuring that there is no diamine vapor in the reaction device and the environment during the reaction, and that the moles of reactants during the reaction The scale does not change. Use of the listed diamines ensures mixing in the liquid reaction medium from start to finish of the reaction, ie effective control of the reaction.

The reaction is preferably carried out with constant mixing of the initial reagents guanidinium salt and DA (diamine) in a molar ratio of 1:1, and the reaction temperature ranges from 140-190° C. depending on the diamine used. For the reaction, conventional pure guanidinium salts (99% purity) were used. As a result, a new polymeric biocide-water-soluble polyoxyalkyleneguanidine salt was prepared based on guanidinium salt, which provided improved bactericidal properties with higher hydrophilicity and outstanding polymeric surface active substance properties. The minimum inhibitory concentration (in %) to Escherichia coli is 0.00008, that is, significantly better than PHMG (polyhexamethylene guanidine); relative molecular mass Mw=13500, higher than PHMG, for rats, toxicity Lower, ie, _LD50 = 3400 mg/kg, while _LD50 = 2500 mg/kg for PHMG.

The results obtained are demonstrated by the following examples, examples 1 to 4 corresponding to the appended table:

Example 1

At room temperature of 20°C, 25.28 g (0.17 mol) of liquid diamine-triethylene glycol diamine (TEDA) (H ₂ N-CH ₂ CH ₂ -O-CH ₂ CH ₂ -O-CH ₂ CH ₂ -NH ₂ ) into a three-necked flask with a capacity of 250ml, which is equipped with a stirring device and an air condenser. Then, 16.34 g (0.17 mol) of powdered guanidine hydrochloride (GHCl) was added to the flask. The flask was heated to 150°C for 5 hours with constant mixing. According to the progress of the reaction, the viscosity of the reaction medium increases with simultaneous evolution of ammonia in gaseous form. In this process state, samples are taken from the reaction apparatus. The resinous yellow product is hydrophilic and dissolves rapidly and completely in water. A dry sample of the product (sample 1a) was weighed, dissolved in water, and its intrinsic viscosity was measured with an Ubbelohde-Viscometer. The result [η]=0.04dl/g indicates that in this reaction state, a polymer product has been formed, and the average amount of its relative molecular mass Mw=2500. The product already has biocidal properties (see table).

Heating was then continued at 170°C for an additional 9 hours while mixing the liquid reaction mixture. At this point, gas generation continues and the viscosity of the reaction medium continues to increase. After the reaction at a temperature of 170°C for the 9 hours, another sample No. 1b) was taken out from the reaction system. The color intensity of the polymer sample increased and became light brown. Measurement of the intrinsic viscosity of this sample 1b) gave [η] = 0.07 dl/g, which corresponds to an average relative molecular mass Mw = 5800, which indicates an increase in the relative molecular mass during the reaction. At the same time, the bactericidal effect is increased, see table. Since gas generation could still be observed after reacting at 170°C for 9 hours, ie, the reaction was not completed, the reaction system was continued to be heated at 170°C for another 4 hours. Then, gas is evolved and the reaction is complete.

Finally, another polymer sample 1c) was taken and its intrinsic viscosity value was measured, [η]=0.085dl/g, which corresponds to a relative molecular mass Mw=9100. The reaction product is rapidly and completely dissolved in water and has remarkable hydrophilicity.

The determination of the individual elemental components of the polymer product yielded the following results:

Measured value (%): C-40.4; 40.25; N-19.7; 19.85; H-7.4; 7.456.

Calcd ₍ %) _{for C7N3O2ClH16} : C-40.1; _N -20.04; H-7.63.

Thus, new polymer products were prepared which corresponded in composition to polytriglycol guanidine hydrochloride. The final product yield for the experiment was 98.7%. It is low toxic, rat oral dose LD ₅₀ =3100 mg/kg, ie has much lower toxicity than PHMG (see table) and high bactericidal activity.

Example 2

As in Example 1, the same starting reagents were added to the reaction flask in the same amount and in the same molar ratio. With constant mixing, the reaction was run from start to finish at 150°C for 25 hours until no more ammonia was evolved. The obtained reaction product is water-soluble, light brown, and the yield is 99.1%. The reaction product corresponds in elemental composition to polyethylene glycol guanidine hydrochloride.

Element composition:

Measured value (%): C-40.7; N-19.65; H-7.6

Calculated value (%): C-40.01; N-20.04; H-7.63

The intrinsic viscosity of this sample (sample 2) was measured to be [η] = 0.11 (Mw - 11800). This sample has higher bactericidal activity and lower toxicity than PHMG.

Example 3

In a three-necked flask with a capacity of 250 ml equipped with a stirring device and an air condenser, add 48 g (0.208 mol) of a material with a molecular weight of 230 of the following structure at 20° C. at room temperature:

and 19 g (0.208 mol) of powdered guanidine hydrochloride (GHCl) in an equimolar amount. With heating under constant mixing, the mixture was heated first at 150°C for 2 hours and then at 170°C for 9 hours. In this state, sample 3a), a hydrophilic, light brown viscous product, was taken from the reaction mixture, and its intrinsic viscosity value was measured: [η]=0.045dl/g, which corresponds to the molecular weight Mw ~ 3000. Then, heating was continued at 170° C. for another 9 hours until no more ammonia was evolved, ie, the reaction was complete. The yield of the final product was 98.9%.

Based on the analytical data for each element, the final product corresponds to the desired structural formula of polyoxypropyleneguanidine hydrochloride.

Measured value (%): C-50.85; N-13.35; H-9.6

Calculated value (%): C-50.4; N-13.57; H-9.69

Measure the reaction final product, the intrinsic viscosity of sample 3b) is [η]=0.12, corresponding to molecular weight Mw - 12500, that is, higher than PHMG.

The bactericidal assay of sample 3b) (Escherichia coli: strain 2590) showed higher biocidal activity and lower toxicity than PHMG (see table).

Example 4

In a three-necked flask with a capacity of 250 ml equipped with a stirring device and an air condenser, add 124.8 g (0.208 mol) of liquid diamine-polyoxyethylenediamine/ Polyoxypropylene:

a+c=2.5, b=8.5

and 19 g (0.208 mol) of guanidine hydrochloride (GHCl).

The reaction mixture was then heated at 150° C. for 25 hours with continuous mixing. Ammonia is released during the reaction, and the viscosity of the reaction system increases. After heating for 25 hours, no more ammonia was evolved, ie, the reaction was complete. The reaction product yield was 99.1%. It is a light brown polymer that dissolves rapidly and completely in water. The intrinsic viscosity of the resulting polymer, sample 4, was measured: [η] = 0.13, which corresponds to the molecular weight Mw ~ 13500, ie, a polymer with such a high molecular weight based on guanidine hydrochloride was synthesized by polycondensation for the first time.

According to the analysis data of each element, the polymer product polyoxyethylene guanidine hydrochloride generated corresponds to the above-mentioned polyoxyethylene structure.

Measured value (%): C-53.1; H-7.85; N-6.95

Calculated value (%): C-52.3; H-7.87; N-7.04

The resulting polymers have lower toxicity and improved bactericidal properties (see table). The resulting polymers also have the notable properties of surface-active polymers.

It has been shown that the measured surface tension value of 32 din/cm for this sample is close to that of the known surface active substance sodium lauryl sulfate. (It must be emphasized that no apparent surface-active signature was determined in the PHMG sample.) This surface-active substance signature makes the biocidal properties of the synthesized polymer products more effective at phase-separated interfaces, especially when used on surfaces. Treatment (disinfection) and its use as a cleaning agent ingredient.

Example 5

Preparation of poly(triethylene glycol)-guanidine dihydrogen phosphate

In a three-necked flask with a capacity of 250 ml equipped with a mechanical stirring device and an air condenser, 47.5 g (0.32 mol) of liquid triethylene glycol diamine (relative molecular mass: 148) was added at room temperature. Then, 50.24 g (0.32 mol) of powdered guanidine dihydrogen phosphate (relative molecular mass: 157) was added into the flask, that is, the molar ratio of the reactants was 1:1. Place the flask containing the liquid reaction mass in an oil bath with a temperature regulator. The reaction mass was heated at 170°C for 11 hours with constant mixing. From the first minute of the thermal conditioning, a large amount of ammonia was released (discoloration of the test paper), proving the progress of the polycondensation reaction. During the reaction, the reaction mass became viscous and foam formation was observed visually. The reaction mixture gradually turned into a white resin whose volume exceeded that of the starting liquid mixture. The reaction was terminated when the evolution of ammonia stopped. After the flask had cooled, the polymer resin was removed from the flask with the aid of a spatula and ground into a powder with a mortar, which was more hydrophobic than polyoxytriglyme hydrochloride, but at the same time dissolved immediately and rapidly in water. The experiment yielded about 84.5 g of final polymer product. The intrinsic viscosity of the prepared polymer was measured in 0.4N aqueous sodium chloride solution at 25°C. The viscosity is: [η]=0.056dl/g.

Elemental analysis of the prepared polymer:

Calculated for C ₇ N ₃ O ₆ PH ₁₈ : C-30.99%, N-15.49%, O-35.42%, P-11.44%, H-6.64%

Measured values: C-31.38%, N-15.25%, P-11.67%, H-6.49%

Analysis proved that the prepared polymer was consistent with the required structure.

The biocidal properties of the prepared polymers were examined. The minimum inhibitory concentration values expressed in units (μg/ml) were determined for the two bacteria. For Escherichia coli this value is 2.1 μg/ml; for Ps aeruginosa it is 6.2 μg/ml. This confirms the high biocidal activity of the prepared polymers. The values of some toxicological properties of the polymers were also examined, the _LD50 (oral) in rats was determined. This value was 3200 mg/kg, demonstrating that the polymer is of low toxicity.

Example 6

Preparation of poly(triethylene glycol)-guanidine carbonate

In a 1 L three-necked flask equipped with a mechanical stirring device and an air condenser, 148 g (1 mol) of liquid triethylene glycol diamine was added at room temperature, and then 121 g (1 mol) of powdered guanidine carbonate was added. With constant mixing, the flask was heated in an oil bath; here a fairly uniform mixing of the reactants occurred. Ammonia is released at 140°C and a violent reaction begins. The starting mixture was kept at this temperature (140° C.) for 15 hours. It then became viscous, transforming into a light yellow foamy mass, the volume of which was significantly greater than that of the starting reaction mass. After the flask had cooled, the polymer resin was removed from the flask with the aid of a spatula and ground into a light-colored powder with a mortar, which was quite hydrophobic. As a result of the experiment, about 232g of limited water-solubility polymer-polytrimethylene glycol guanidine carbonate was obtained, and the intrinsic viscosity was: [η]=0.065dl/g (measured in 25°C, 0.4N aqueous sodium chloride solution)

Elemental analysis of the prepared polymer:

Calculated _{for C8N3O5H17} : C- _40.85 %, N- _17.87 %, O-34.04%, H-7.23%

Measured value: C-41.31%, N-17.65%, H-7.03%

Analysis demonstrated that the experimental results agreed with the calculated values as expected.

The minimum inhibitory concentration value (μg/ml) against Escherichia coli was determined for the prepared polymer—polytrigidylglycol guanidine carbonate. The minimum inhibitory concentration (MHK) value was 20 mg/ml, demonstrating the biocidal activity of the prepared polymer.

surface

Properties of Synthesized Polyoxyalkyleneguanidine Hydrochloride sample number Intrinsic viscosity [η] = dl/g measured in 0.1n sodium chloride aqueous solution at 25°C The average amount of relative molecular mass Mw= Bactericidal activity, minimum inhibitory concentration MHK, expressed in % (Escherichia coli, strain 2590) Toxicity Oral LD ₅₀ mg/kg (rat) Prototype 0.1 10000 0.0007 2500 1a) 0.04 2500 0.003 1b) 0.07 5800 0.0015 1c) 0.085 9100 0.001 3000 2 0.11 11800 0.0003 3100 3a) 0.045 3000 0.002 3b) 0.12 12500 0.0001 3150 4 0.13 13500 0.00007 3250

Claims (8)

1. A guanidine derivative based on a biocidal polymer of a diamine comprising an oxyalkylene chain between two amino groups, characterized in that the guanidine derivative is a polycondensation product of an acid addition salt of guanidine and a diamine, The diamine has a polyoxyalkylene chain between two amino groups. 2. The guanidine derivative of the biocidal polymer according to claim 1, characterized in that the use of triethylene glycol diamine with a relative molecular mass of 148 and a relative molecular mass of 230 as representative of numerous polyoxyalkylene guanidine salts The polyoxypropylene diamine and those with a relative molecular mass of 600 polyoxyethylene diamine. 3. use the diamine that comprises polyoxyalkylene chain between two amino groups to prepare the method for polyoxyalkylene guanidine salt in liquid medium, it is characterized in that liquid diamine and guanidine salt are in liquid diamine medium, At a temperature of 140-190° C., under continuous mixing from the beginning of the reaction to the completion of the reaction, polycondensation is carried out for 9-16 hours depending on the diamine used, and the polycondensation reaction is carried out at an initial molar ratio of reactants of 1:1. 4. The method for preparing polyoxyalkylene guanidine hydrochloride is characterized in that using guanidine hydrochloride and having the liquid diamine of polyoxyalkylene between two amino groups, reactant initial molar ratio is 1: 1. In a liquid diamine medium, under continuous mixing from the beginning of the reaction to the completion of the reaction, at a temperature of 150-170°C, perform polycondensation for 18-25 hours depending on the diamine used. 5. The method according to claim 4, characterized in that the interaction between guanidine hydrochloride and triethylene glycol diamine with a relative molecular mass of 148 is carried out as follows: start to act at 150° C. for 5 hours, then act at 170° C. for 13 hours; or Act at 150°C for 25 hours. 6. The method according to claim 4, characterized in that the interaction of guanidine hydrochloride and polyoxypropylene diamine with a relative molecular mass of 230 is carried out as follows: 150° C. for 2 hours, then 170° C. for 18 hours. 7. Process according to claim 4, characterized in that the interaction of guanidine hydrochloride and polyoxyethylenediamine with a relative molecular mass of 600 is carried out as follows: 25 hours at 150°C. 8. Biocidal polymers prepared according to the process according to one of claims 3-7.